rs2715554

Positions:

• chr17-40332918-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000254066.10(RARA):​c.178+1522A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,286 control chromosomes in the GnomAD database, including 1,026 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (1026 hom., cov: 33)
• Consequence: RARA ENST00000254066.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.844

Genes affected

RARA (HGNC:9864): (retinoic acid receptor alpha) This gene represents a nuclear retinoic acid receptor. The encoded protein, retinoic acid receptor alpha, regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of development, differentiation, apoptosis, granulopoeisis, and transcription of clock genes. Translocations between this locus and several other loci have been associated with acute promyelocytic leukemia. Alternatively spliced transcript variants have been found for this locus.[provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RARA	NM_000964.4	c.178+1522A>G		intron_variant		ENST00000254066.10	NP_000955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RARA	ENST00000254066.10	c.178+1522A>G		intron_variant		1	NM_000964.4	ENSP00000254066	P4
RARA	ENST00000425707.7	c.178+1522A>G		intron_variant		1		ENSP00000389993
RARA	ENST00000394089.6	c.178+1522A>G		intron_variant		2		ENSP00000377649	P4
RARA	ENST00000577646.5	c.178+1522A>G		intron_variant		5		ENSP00000464287

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15028 AN: 152168 Hom.: 1026 Cov.: 33

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0684

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0656

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0986 AC: 15020 AN: 152286 Hom.: 1026 Cov.: 33 AF XY: 0.0949 AC XY: 7068 AN XY: 74462

Gnomad4 AFR AF: 0.0295

Gnomad4 AMR AF: 0.0683

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0654

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.101

Alfa AF: 0.132 Hom.: 1839

Bravo AF: 0.0910

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.38
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2715554; hg19: chr17-38489170;